Murine acid alpha-glucosidase - Cell-specific mRNA differential expressionduring development and maturation

Acid cy-glucosidase (GAA) cleaves the alpha 1-4 and alpha 1-6 glycosidic li nkages of glycogen and related alpha-glucosyl substrates within lysosomes, Its deficiency results in glycogen storage disease type II (GSDII) variants including Pompe disease. To gain insight into the tissue patterns of invol vement by glycogen storage in GSDII, GAA mRNA expression in mouse tissues w as evaluated by Northern blot and in situ hybridization analyses. Extensive temporal and spatial variation of GAA mRNA was observed, During preterm ma turation, GAA mRNA levels of whole mice progressively increased as assessed by Northern analysis, By ill situ hybridization with GAA antisense mRNA, l ow signals were detected in most tissues throughout gestation, However, inc reased expression in specific cell types of different tissues was observed beginning at 16 days post coitum in developing brain neurons, primitive inn er ear cells, and seminiferous tubular epithelium, In adult mice, whole-org an GAA mRNA levels were highest in brain, moderate in heart, liver, and ske letal muscle, and lowest in the series kidney > lung > testis > spleen. By in situ hybridization, the highest-intensity signals were in neurons of the central and peripheral nervous systems whereas neuroglial cells had only l ow-level signal. Signals of moderate intensity were in cardiomyocytes where as low signals were in hepatocytes and skeletal muscle myocytes and very lo w in cells of the lungs, thymus, pancreas, spleen, and adrenal glands, Howe ver, testicular Sertoli cells and kidney tubular epithelial cells had signi ficant signals even though surrounding cells had very low signals. The disc rete temporal and spatial variations of GAA mRNA during development indicat e different physiological roles for this enzyme in various cell types and d evelopmental stages.